The objective of this project is to examine neuronal and non-neuronal cell populations located within the spinal trigeminal system in response to several modalities of orofacial pain. Questions that we wish to address are: 1) what changes occur in the central nervous system immediately following dental trauma? 2) How is this different from other models of inflammation? 3) Are there any permanent changes in the morphology or functionality of cells within the spinal trigeminal system and if so, what are their implications? and 4) What effect do neurotransmitters have on orofacial wound healing? Specific aims include: 1) Determine the short term neurochemical changes that occur within the spinal trigeminal nucleus and ganglion following dental extraction, H) Determine whether long term morphological and functional changes exist in trigeminal system following dental trauma. III) Determine the effects of transection of the maxillary branch of trigeminal nerve (V2) on long term changes in spinal trigeminal plasticity and pain transmission, & IV) Determine morphological and functional changes in spinal trigeminal nuclei and ganglia following induction of orofacial inflammation. Three paradigms for development of orofacial pain include unilateral extraction of incisors, inflammation of mystacial pad, & ligation/ axotomyof maxillary division of the trigeminal nerve. Following induction of pain, trigeminal nuclei and ganglia will be harvested and immunohistochemical analysis performed using a battery of markers for activation of nociceptive afferent fibers, neuronal activation, axonal regeneration, and cellular reorganization. Understanding the central and peripheral changes that occur following orofacial trauma will allow us to further elucidate the role of peptidergic neurotransmitters in pain transmission, inflammation, and wound healing. Additionally, the discovery and development of novel therapeutic drugs aimed at alleviating orofacial pain conditions not relieved by traditional analgesics may be made possible with results gained from these experiments. Key Words: Substance P, trigeminal, pain